Severe graft v. host disease (GVHD) occurs in patients grafted with HLA-compatible marrow cells but not in mice rafted with allogeneic H-2-compatible marrow cells. We were able to create a mouse model reflecting the clinical GVHD by infusing irradiated spleen cells differing in H-2 with donor and hot six times after cell transfer. This reflected the clinical proceduring of infusing irradiated blood products from donors not matched for HLA with the hosts. We propose to utilize this model to study the mechanism of GVHD; in particular we wish to determine which immune cell types in the irradiated spleen cell inocula and in the marrow which interact to cause GVHD. The nature of the cytotoxic effector cells generated in the GVHD will be studied. To determine if GVHD may have more than one mechanism, advantage will be taken of the facts that autoimmune NZB mice have spleen cells deficient in GVH cells for neonatal unirradiated mice but extremely potent in irradiated adult hosts. In vivo correlates of the GVHD will be evaluated.